Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Work by researchers at MRC HIU zeroes in on the mechanisms by which T cells respond to Salmonella infections.

© David Goulding, Wellcome Trust Sanger Institute (CC BY-NC 4.0)

Enteric fever (also known as typhoid fever) is a life-threatening infection caused by the bacteria Salmonella Typhi and Paratyphi, usually through ingestion of contaminated food or water. The acute illness is characterized by prolonged fever, headache, nausea, loss of appetite, and constipation or sometimes diarrhoea. This disease is responsible for around 20 million new infections and 150,000 deaths each year, mainly in South and South-East Asia and Africa. Despite its impact, a vaccine able to protect against all types of Salmonella is still lacking.

In a study published this week in Nature Immunology researchers in the Cerundolo group, led by Giorgio Napolitani, at the MRC Human Immunology Unit (Radcliffe Department of Medicine), in collaboration with the Oxford Vaccine Group, and the Singapore Immunology Network used a combination of techniques to make important advances in understanding how the immune system responds to these pathogens. One of the major hurdles in the development of vaccines against enteric fever is that Salmonella Typhi and Salmonella Paratyphi infect only humans, so the disease cannot be studied in laboratory animals. To overcome this issue, researchers at the Oxford Vaccine Group deliberately infected volunteers with the bacteria, so that they could study how the immune system copes with the infection.

The team at the MRC Human Immunology Unit particularly focused on a type of immune cell thought to play a major protective role against Salmonella, called CD4 positive T cells. The authors were able to isolate and characterize individual immune cells from the blood of infected volunteers, and looked for those that were able to recognise different types of Salmonella. Using this ground-breaking approach, the Oxford team could reconstruct the immune response to Salmonella in a dish. They discovered that some T cells can recognise many different types of Salmonella, while others were very selective and could recognise the very small differences that distinguish the two different types of Salmonella bacteria which cause enteric fever. “We were surprised to find that, despite these bacteria containing more than 4,000 proteins, during infection most of the T cells recognize only a handful of Salmonella proteins, and variation of a single amino-acid  in these proteins can make a difference in whether some T cells can recognize or not these bacteria.”, said Dr Napolitani.

This careful study paves the way for the design of better, and wider ranging, vaccines against Salmonella bacteria. “Our work has led to the identification of the distinct Salmonella proteins that different T cells are able to detect. This knowledge will help design better vaccines against these pathogens in the future” said Prof Cerundolo.

This work was funded by an Experimental Medicine Challenge Grant from the Medical Research Council.

 

Clonalanalysis.png

Similar stories

Mechanism behind repair of cancer-inducing mutations discovered

New Nature paper uncovers the precise mechanism behind how the BRCA1 protein detects and engages with DNA breaks in the genome, helping to prevent the development of breast and ovarian cancers.

DNA breakthrough could help identify why some people are more affected by Covid-19

Scientists from the MRC Weatherall Institute of Molecular Medicine have developed a method that allows them to see, with far greater accuracy, how DNA forms large scale structures within a cell nucleus.

New clinical trial for patients affected by blood cancer

Radcliffe Department of Medicine's Professor Adam Mead is leading PROMise, a new clinical trial offering a novel treatment option for patients with a type of blood cancer called myelofibrosis.

Immune cells imperfect at distinguishing friend from foe

When it comes to distinguishing a healthy cell from an infected one that needs to be destroyed, the immune system’s killer T cells sometimes make mistakes. This discovery, described today in the journal eLife, upends a long-held belief among scientists that T cells were nearly perfect at discriminating friend from foe. The results may point to new ways to treat autoimmune diseases that cause the immune system to attack the body, or lead to improvements in cutting-edge cancer treatments.

Professor Graham Ogg elected Academy of Medical Sciences Fellow

Fellows are selected for their exceptional contributions to the advancement of medical science through innovative research discoveries and translating scientific developments into benefits for patients and the wider society.